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GSE50824
Mus musculus
19 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
It is generally believed that cerebellar granule neurons originate exclusively from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here we identify a rare population of neuronal progenitors in the developing cerebellum that expresses Nestin. Although Nestin is widely considered a marker for multipotent stem cells, these Nestin-expressing progenitors (NEPs) are committed to the granule neuron lineage. Unlike conventional GNPs, which reside in the outer EGL and proliferate extensively, NEPs reside in the deep part of the EGL and are quiescent. Expression profiling reveals that NEPs are distinct from GNPs, and in particular, express markedly reduced levels of genes associated with DNA repair. Consistent with this, upon aberrant activation of Sonic hedgehog (Shh) signaling, NEPs exhibit more severe genomic instability and give rise to tumors more efficiently than GNPs. These studies identify a novel progenitor for cerebellar granule neurons and a novel cell of origin for medulloblastoma.
Publication Title
A population of Nestin-expressing progenitors in the cerebellum exhibits increased tumorigenicity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem-like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies.
Publication Title
Nestin Mediates Hedgehog Pathway Tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 13 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Young adult N2 Caenorhabditis elegans were infected with Enterococcus faecalis or Enterococcus faecium for 8 h to determine the transcriptional host response to each enterococcal species.
Publication Title
Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Cohesinopathies are characterized by mutations in the cohesin complex. Mutations in NIPBL, a cohesin loader, result in Cornelia de Lange syndrome (CdLS). CdLS is a congenital genetic disorder distinguished by craniofacial dysmorphism, abnormal upper limb development, delayed growth, severe cognitive retardation, and multiple organ malformations.It has been suggested that CdLS is caused by defects in the cohesin network that alter gene expression and genome organization. However, the precise molecular etiology of CdLS is largely unclear. To gain insights, we sequenced mRNAs isolated from mouse embryonic fibroblasts of both WT and NIPBL-haploinsufficient mice and compared their transcriptomes. Overall design: Examination of gene expression of WT and NIPBL+/- mice by RNA-seq
Publication Title
NIPBL Controls RNA Biogenesis to Prevent Activation of the Stress Kinase PKR.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Condensin complexes are highly conserved for chromosome compaction to ensure their faithful segregation in mitosis. Condensin II is present in the nucleus throughout the cell cycle, including interphase. The aim of these experiments is to investigate the changes of gene expression in knockdown of NCAPH2, a condensin II subunit, in mouse embryonic stem cells compared to their control cells. Overall design: Examination of gene expression of controls and NCAPH2 knockdown cells by RNA-seq
Publication Title
Condensin II is anchored by TFIIIC and H3K4me3 in the mammalian genome and supports the expression of active dense gene clusters.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Salt stress is one of the most severe environmental conditions which cause huge losses in crop production worldwide. We identified a novel calcium-binding protein and used the Affymetrix whole-genome arrays to define downstream targets of this important protein.
Publication Title
A nuclear calcium-sensing pathway is critical for gene regulation and salt stress tolerance in Arabidopsis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Total gene expression analysis was performed on RNA from testes extracted from two litters of constitutive homozygous and heterozygous H3f3b knockout mice compared to WT littermates.
Publication Title
Histone H3.3 regulates dynamic chromatin states during spermatogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 60 Downloadable Samples
Description
We investigated the occupancy of RNA PolII and INTS11 during the stimulation of EGF and compared with drug treated condition using inhibitors against MAPK pathway and Integrator. Additionally, we examined transcription by sequencing the chromatin-bound fraction of RNA. Overall design: We employed several cel lines in our experiment, including HELA, KRAS mutant lung cancer cell line A549 and BRAF mutatant melanoma cell line A375. The conditons we checked including EGF stimulation, MAPK pathway inhibition using BRAF, MEK or ERK inhibitiors, targeting INTS11 with RNAi or integrator inhibitor. We used RNA sequencing to measure the expression profile and CHIP sequencing to detect INTS11 and RNA PolII recruitment on chromatin.
Publication Title
Integrator orchestrates RAS/ERK1/2 signaling transcriptional programs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The observation that Tcf3 (MGI name: Tcf7l1) bound the same genes as core stem cell transcription factors, Oct4 (MGI name:Pou5f1), Sox2 and Nanog, revealed a potentially important aspect of the poorly understood mechanism whereby Wnts stimulate self renewal of pluripotent mouse embryonic stem (ES) cells. Although the conventional view of Tcf proteins as the -catenin-binding effectors of Wnt signaling suggested Tcf3 should activate target genes in response to Wnts, here we show that Wnt3a and Tcf3 effectively antagonize each others effects on gene expression. Genetic ablation of Tcf3 caused similar effects as treating cells with recombinant Wnt3a.
Publication Title
Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Identifying the early gene program induced by GnRH would help understand how GnRH-activated signaling pathways modulate gonadotrope secretory response. We previously analyzed GnRH-induced early genes in LbT2 cells, however these lack GnRH self-potentiation, a physiological attribute of gonadotropes. To minimize cellular heterogeneity, rat primary pituitary cultures were enriched for gonadotropes by 40-60% using a sedimentation gradient. Given the limited number of gonadotropes, RNA was amplified prior to microarray analysis. Thirty-three genes were up-regulated 40 minutes after GnRH stimulation. Real-time PCR confirmed regulation of several transcripts including fosB, c-fos, egr-2 and rap1b, a small GTPase and member of the Ras family. GnRH stimulated rap1b gene expression in gonadotropes, measured by a sensitive single cell assay. Immunocytochemistry revealed increased Rap1 protein in GnRH-stimulated gonadotropes. These data establish rap1b as a novel gene rapidly induced by GnRH and a candidate to modulate gonadotropin secretion in rat gonadotropes.
Publication Title
Optimized amplification and single-cell analysis identify GnRH-mediated activation of Rap1b in primary rat gonadotropes.
Sample Metadata Fields
Sex, Specimen part
View Samples